Track topics on Twitter Track topics that are important to you
The investigators hypothesize that ß1-RB attenuates ECM degradation and progressive adverse LV remodeling and failure in the volume overload of MR. Patients without coronary artery disease and moderate MR, as assessed by color/flow Doppler echocardiography, will be randomized to ß1-RB vs. placebo to address the following aims:
*Aim 1: Establish whether Beta1-RB attenuates adverse LV remodeling compared to placebo in patients with non-surgical, chronic MR. Using 3-dimensional magnetic resonance imaging (MRI) and tissue tagging, LV function and geometry will be assessed at baseline and every 6 months for up to 2 years.
Aim 2: Determine whether indices of inflammation correlate with degree of LV remodeling and whether ß1-RB decrease indices of inflammation and collagen turnover. At the time of MRI, blood samples for collagen breakdown products, MMP activity, and markers of excess production of RIS will be obtained and related to changes in LV remodeling defined by serial 3-dimensional MRI and tissue tagging.
In Western society, the most common causes of chronic mitral regurgitation (MR) are ischemic heart disease and myxomatous degeneration of the valve, resulting in prolapse, ruptured chordae or partial flail leaflet. Current indications for surgery are only for patients with severe MR and either notable symptoms or overt LV dysfunction (ejection fraction < 60%, end-systolic diameter > 40 mm). Therefore, despite the availability of surgery, most patients with MR of moderate severity are not immediate candidates for surgery, warranting analysis of potential beneficial effects of medical treatment. Chronic therapy with vasodilators reduces LV wall stress and thereby delays the need for valve replacement in aortic regurgitation; however, no such data are currently available in patients with chronic MR using standard vasodilators or agents that block the renin angiotensin system (RAS).
In a clinically-relevant dog model of MR, the investigators have shown increased LV ACE and chymase expression, increased LV angiotensin II but, as opposed to pressure overload, there was an absence of fibrosis with net extracellular matrix (ECM) degradation and activation of matrix metalloproteinases (MMPs). However, blockade of the RAS does not improve (and may actually exacerbate) LV remodeling in MR. Interestingly, the investigators and others have shown that ß1-receptor blockade (ß1-RB) is more effective than RAS blockade in attenuating progressive LV remodeling and ECM degradation in MR. Moreover, increased sympathetic drive and inflammation has been identified in patients with chronic MR. ß-RB reduced plasma markers of inflammation in patients with heart failure and resulted in substantial reverse LV remodeling in patients with heart failure. Taken together, activation of the adrenergic nervous system early in the course of volume overload contributes to increased production of reactive inflammatory species (RIS) and that one mechanism underlying the salutary effects of ß-blockade may relate to attenuation of myocardial formation of RIS with subsequent beneficial effects on MMP activation and ECM and LV remodeling and function.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Beta-1 receptor blocker Metoprolol
University of Alabama at Birmingham
Active, not recruiting
University of Alabama at Birmingham
Published on BioPortfolio: 2014-07-23T21:11:03-0400
Mitral valve regurgitation (leakage of the mitral valve of the heart) is frequent and currently there is no specific medical therapy. Mitral regurgitation is a slowly progressive disease ...
The purpose of this study tests whether a beta-blocker drug will benefit patients with chronic mitral regurgitation.
Prospective, observational, multi-center trial in which patients with mitral regurgitation sufficient to merit mitral valve repair will receive a surgical transvalvular, intra-annular Mitr...
Use of beta-blockers has proven beneficial in patients with hypertension, heart failure, and in people who have suffered a heart attack. The use in patients who have Chronic Obstructive Pu...
Beta-blocker medications have been shown to improve heart function and prolong the lives of patients with chronic heart failure (CHF). Some people with advanced CHF have difficulty taking...
Mitral regurgitation is the most common valve disease in the United States. This article focuses on a new percutaneous mitral valve treatment for chronic degenerative mitral regurgitation.
To determine the prevalence of mitral regurgitation (MR) in a large cohort of consecutive patients undergoing clinically indicated echocardiography and to examine the distribution of primary and secon...
Mitral annuloplasty (MAP) for ischemic mitral regurgitation (IMR) with advanced remodeling is often associated with recurrent mitral regurgitation (MR). We performed surgeries adjusted according to th...
The free margin running suture (FMRS) is a novel technique for nonresection correction of degenerative mitral regurgitation. It was employed in 37 minimally invasive mitral repair cases. We performed ...
The patho-etiology of mitral regurgitation (MR) has been suggested as a mediator of outcomes following mitral valve (MV) operations, particularly in ischemic functional mitral regurgitation (IMR). Thi...
Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.
A cardioselective ADRENERGIC BETA-1 RECEPTOR ANTAGONIST (beta-blocker) that functions as a VASODILATOR through the endothelial L-arginine/ NITRIC OXIDE system. It is used to manage HYPERTENSION and chronic HEART FAILURE in elderly patients.
Hydrogenated alprenolol derivative where the extra hydrogens are often tritiated. This radiolabeled form of ALPRENOLOL, a beta-adrenergic blocker, is used to label the beta-adrenergic receptor for isolation and study.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). beta-1 Adrenergic receptors are equally sensitive to epinephrine and norepinephrine and bind the agonist dobutamine and the antagonist metoprolol with high affinity. They are found in the heart, juxtaglomerular cells, and in the central and peripheral nervous systems.
Abnormal protrusion or billowing of one or both of the leaflets of MITRAL VALVE into the LEFT ATRIUM during SYSTOLE. This allows the backflow of blood into left atrium leading to MITRAL VALVE INSUFFICIENCY; SYSTOLIC MURMURS; or CARDIAC ARRHYTHMIA.
Cardiology is a specialty of internal medicine. Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...
Radiology is the branch of medicine that studies imaging of the body; X-ray (basic, angiography, barium swallows), ultrasound, MRI, CT and PET. These imaging techniques can be used to diagnose, but also to treat a range of conditions, by allowing visuali...